Epithelial maturity influences EPEC-induced desmosomal alterations.

Desmosomes are junctional protein complexes that confer strong adhesive capacity to adjacent host cells. In a recent study, we showed that enteropathogenic Escherichia coli (EPEC) disrupts desmosomes, weakens cell-cell adhesion and perturbs barrier function of intestinal epithelial (C2BBe) cells. Desmosomal damage was dependent on the EPEC effector protein EspH and its inhibitory effect on Rho GTPases. EspH-mediated Rho inactivation resulted in retraction of keratin intermediate filaments and degradation of desmosomal cadherins. Immunofluorescence studies of EPEC-infected C2BBe cells revealed keratin retraction towards the nucleus coincident with significant cytoplasmic redistribution of the desmosomal cadherin desmoglein-2 (DSG2). In this addendum, we expand on how EPEC-induced keratin retraction leads to loss of DSG2 anchoring at the junctions, and show that maturity of the epithelial cell monolayer impacts the fate of desmosomes during infection.

Desmosomes are unaltered during infections by attaching and effacing pathogens.

The human attaching and effacing (A/E) intestinal pathogens enterohemorrhagic Escherichia coli (EHEC), enteropathogenic E. coli (EPEC), and the murine A/E pathogen Citrobacter rodentium cause serious diarrhea in their hosts. These bacteria alter numerous host cell components, including organelles, the host cell cytoskeleton, and tight junctions during the infectious process. One of the proteins that contribute to the intermediate filament network in host cells, cytokeratin-18, is extensively altered during EPEC infections. Based on this, we tested the hypothesis that desmosomes, the only intercellular junctions that interact with intermediate filaments, are also influenced by A/E pathogen infections. We found that the desmosomal transmembrane proteins desmoglein and desmocollin, as well as the desmosome plaque protein desmoplakin, all remain unchanged during EPEC infection in vitro. This evidence is corroborated by the unaltered localization of desmoglein and desmoplakin in vivo in mice infected with C. rodentium for 7 days. Electron microscopic analysis of 7-day C. rodentium-infected murine colonocytes also show no observable differences in the desmosomes when compared to uninfected controls. Our data suggest that, unlike tight junctions, the desmosome protein levels and localization, as well as desmosome morphology, are unaltered during A/E pathogenesis.

Pseudomembranous oral candidiasis in HIV infection: ultrastructural findings.

A light and electron microscopic investigation of pseudomembranous candidiasis in HIV infection was undertaken as there is little data available on the ultrastructural features of the invasive phase of Candida in this disease. On examination of biopsy specimens of four patients, histopathology revealed the classic features of superficial candidiasis, including hyphal penetration down to the spinous cell layer, parakeratosis, acanthosis and spongiosis of the infected, superficial epithelium. However, in one case, hyphae traversed the entire epithelium and crossed the basal membrane, invading the adjacent connective tissue. Ultrastructural investigations revealed initial hyphal penetration through the intercellular spaces, possibly demonstrating thigmotropism. However, hyphal penetration was not solely confined to intercellular spaces, as some specimens demonstrated hyphal elements traversing both the cytoplasm and the nuclei of the spinous cells. In these areas of the epithelium appressoria-like appendages were often found at the hyphal tip. These phenomena, commonly described in plant fungi, have rarely been described in human material. Pools of desmosomes were seen in the vicinity of the hyphal pathways, implying that the penetration procedure is associated with detachment and congregation of desmosomes, possibly by enzymatic means. Interestingly, the host immune response to fungal invasion appeared to be minimal, as no immune-effector cells were seen closely associated with either the blastospores or the hyphae in any of the tissues examined. Whether the foregoing events are exaggerated by the abortive immune response seen in HIV-infected patients, or common in immunocompetent individuals during candidal invasion of epithelia, needs to be ascertained by further studies.